Intestinal Peyer’s Patches: Structure, Function, and In Vitro Modeling

Abstract

Backgound: Considering the important role of the Peyer’s patches (PPs) in gut immune balance, understanding of the detailed mechanisms that control and regulate the antigens in PPs can facilitate the development of immune therapeutic strategies against the gut inflammatory diseases. Methods: In this review, we summarize the unique structure and function of intestinal PPs and current technologies to establish in vitro intestinal PP system focusing on M cell within the follicle-associated epithelium and IgA + B cell models for studying mucosal immune networks. Furthermore, multidisciplinary approaches to establish more physiologically relevant PP model were proposed. Results: PPs are surrounded by follicle-associated epithelium containing microfold (M) cells, which serve as special gateways for luminal antigen transport across the gut epithelium. The transported antigens are processed by immune cells within PPs and then, antigen-specific mucosal immune response or mucosal tolerance is initiated, depending on the response of underlying mucosal immune cells. So far, there is no high fidelity (patho)physiological model of PPs; however, there have been several efforts to recapitulate the key steps of mucosal immunity in PPs such as antigen transport through M cells and mucosal IgA responses. Conclusion: Current in vitro PP models are not sufficient to recapitulate how mucosal immune system works in PPs. Advanced three-dimensional cell culture technologies would enable to recapitulate the function of PPs, and bridge the gap between animal models and human.

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“…Therefore, the immune responses in the intestinal tract, where they are first absorbed by the body, and intestinal immunity, including the Peyer’s patches, are very important. When cells within Peyer’s patches are activated, cytokines are produced, which activate B lymphocytes to differentiate into plasma cells and induce IgA secretion [ 38 ]. IgA plays a central role in the intestinal immune system, as it inhibits the attachment of various harmful substances and pathogenic microorganisms in the intestinal tract to the mucosal epithelium and possesses antibody activities against bacteria and viruses entering the intestinal tract.…”

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“…PP consists of hundreds of lymphoid follicles surrounded by follicle-associated epithelium containing M cells and is predominantly found in the distal ileum. 109 The PP is an important lymphoid organ for bacterial colonization and activation of T cell-dependent IgA signals. 110 , 111 Bacteria clustered on the surface of the PP are predominantly Serratia and Lactobacillus spp , while, those clustered inside the PP are mainly Alkalobacter spp and Pallobacterium spp .…”

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“…Figure displays an outline of the different primary and lymphoid tissue‐based responses in the gut. [ 44 ]…”